Down syndrome (DS) is the most common genetic cause of intellectual disability but the neuroanatomical abnormalities that contribute to specific cognitive deficits in individuals with DS have not been well defined. Histopathological observations, though limited, have consistently implicated reduced neuron number as a major defect in the DS cerebral cortex. Yet the identity of the neuron subtype that is affected is not known and this lack of information lessens both our knowledge of DS neuropathology and our ability to define potential therapies. It is therefore critical to our understanding of the neurobiological basis of intellectual disability in DS to define the neurons that are reduced in DS cerebral cortex. This small self-contained proposal aims to test the simple hypothesis that there are fewer interneurons in human DS cortex. Inhibitory interneurons will be identified and counted in post-mortem DS human brain and compared to controls using modern techniques for immunostaining and quantification.